Storage and dispensing devices for administration of oral transmucosal dosage forms

ABSTRACT

Dispensing devices and systems for oral transmucosal administration of small volume drug dosage forms to the oral mucosa are provided. The dispensing device may be a single dose applicator (SDA), or an electromechanical device comprising a means for patient identification such as a wrist worn RFID tag and annular bidirectional antenna together with a lock-out feature.

CROSS REFERENCE TO OTHER APPLICATIONS

This application is a continuation of and claims priority to U.S.application Ser. No. No. 12/724,634, filed Mar. 16, 2010, entitled,“Storage and Dispensing Devices for Administration of Oral TransmucosalDosage Forms,” which claims priority to and the benefit of U.S.Provisional Application Ser. No. 61/161,267, filed Mar. 18, 2009,entitled, “Storage and Dispensing Devices for Administration of OralTransmucosal Dosage Forms,” each of which is incorporated by referenceherein in its entirety.

FIELD OF THE INVENTION

The present invention relates to dispensing devices and systems for oraltransmucosal administration of small volume drug dosage forms (tablets)to the oral mucosa. The dispensing device may be a single doseapplicator (SDA) or an electromechanical device comprising a wrist wornRFID tag and annular bidirectional antenna.

BACKGROUND OF THE TECHNOLOGY

Many medications that are dosed “as-needed” in a hospital orinstitutional setting require a restricted dosing schedule for safeself-administration.

Intravenous (IV) patient controlled analgesia (PCA) pumps are typicallyused to administer medications, such as opioids, for treatment of painin the hospital or institutional setting, as well as on an outpatientbasis. Using a preprogrammed PCA pump, the patient receives each dose ofintravenous medication by activating a bedside button at allowable timeintervals. If the button is activated during a time interval in which anallowable dose has already been administered, the pump is “locked out”and unable to deliver the dose until the appropriate time interval haspassed. This prevents the patient from taking more than a maximumallowable dose of medication during a measured time interval.

There is a current focus on patient safety in medication administration,and the Institute for Safe Medication Practices (ISMP) and the JointCommission on the Accreditation of Healthcare Organizations (JCAHO) haveidentified several consistently problematic areas in the use of IV PCA,the most problematic being human and pump errors, examples of whichinclude pump programming errors based on entry of the wrong medicationconcentration; confusion over milligrams versus milliliters; the loadingdose programmed as a bolus dose; the incorrect lockout time selected;and a PCA bolus dose confused with the basal rate. Also problematic isPCA by proxy, where the PCA button is activated by someone other thanthe patient, most commonly family members, nurses; or friends. See,e.g., Hicks, et al., Joint Commission on Quality and Patient Safety,34(12), 734-742, 2008.

Oral mucosal drug delivery is an alternative method of systemic drugdelivery that offers several advantages over both injectable, e.g., IV,and traditional oral routes of administration. The oral mucosa is highlyvascularized, allowing lipophillic drugs to be readily absorbed throughthe oral mucosa and directly enter the systemic circulation, bypassingthe gastrointestinal (GI) tract and first-pass metabolism in the liver.

Many medications have been evaluated for oral transmucosal delivery,however, few are commercially available. Further, although dispensingdevices are available for the administration of a variety of types ofmedications, only inhaled medications are typically administered thoughthe mouth using a device.

In addition, young children are vulnerable to inadvertent exposure tomedications, in particular, when medications are not stored securely.Child-resistant packaging is required for many prescription medicationsas well as many household products. Child-resistant packaging togetherwith “smart” packaging, has resulted in enhanced patient safety. “Smart”packaging or packaging-identification technology such as Radio FrequencyIdentification (RFID) tags provide a viable means of medical-packagingtraceability. RFID technology can provide controlled access tomedications and help ensure patient safety and compliance.

SUMMARY OF THE INVENTION

Controlled access medication dispensers are provided by the claimedinvention.

A radio frequency identification (RFID) system for patientidentification is provided. The system comprises a handheld devicehaving an RFID reader antenna, and a matching wrist worn RFID tag orinlay consisting essentially of a die or chip, a circuit and an antenna,wherein the antenna comprises annular conductors that circumvent thewrist. The antenna field has an axis directed at the patient's hand,such that patient identification occurs when a handheld devicecomprising the reader antenna is held in the patient's hand, resultingin activation of the reader antenna.

The wrist worn RFID tag or inlay may be a bracelet and the RFID signalmay be directional and symmetrical or bidirectional, but notsymmetrical. In one embodiment, the distance between the handheld deviceand the wrist worn RFID tag or inlay is between 0 inches and 12 inches,between 0 and 8 inches, or between 0 and 6 inches.

Further provided is a drug dispensing system having a patientidentification feature comprising the RFID system described hereinaboveand methods of using the same.

In one embodiment, when the wrist worn RFID tag is removed, the RFID tagor inlay is damaged or destroyed and the drug dispensing system becomesnon-functional.

In another embodiment, the dispensing device is activated and dispensesa drug dosage form following patient identification.

In yet another embodiment, the drug dispensing device system furthercomprises small volume drug dosage forms and a timed lock-out feature,wherein the timed lock-out feature provides for a set lock-out time, andthe dispensing device cannot be activated during the set lock-out time.

The drug dispensing device system may further comprise asufentanil-containing drug dosage form for use in the inpatient/hospitalsetting or in the outpatient setting.

In one further embodiment, methods for controlled access and safeadministration of sufentanil to the oral mucosal membrane of a subjectin the outpatient setting are provided.

In one aspect of this embodiment, a multiple single-dose dispenser (MSD)containing a plurality of single dose applicators (SDAs) is provided.Each SDA comprises a drug dosage form with an amount of sufentanilselected from the group consisting of 5 mcg, 10 mcg, 15 mcg, 20 mcg, 30mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and 100 mcg, wherein thedrug dosage forms have a volume of less than 30 microliters or a mass ofless than 30 mg.

The MSD may comprise one or more of the following features: (i) alock-out feature adapted for setting a lock-out time such that an SDAcannot be removed from the MSD during the lock-out time; (ii) a dosecounting feature; (iii) a patient identification feature such as RFID;and (iv) a child resistant feature.

Each SDA may comprise: (i) two case halves that house the drug dosageform; (ii) a label designed to provide for child resistance; (iii) apusher; and (iv) a bridge feature that breaks away as the pusher isadvanced to deliver a drug dosage form to the oral mucosal membrane.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a photograph of a handheld and portable drug dispensing deviceand corresponding and RFID bracelet.

FIG. 2 is a photograph of a handheld and portable device comprised of adisposable dispensing end, a reusable controller end and a disposabledrug cartridge.

FIGS. 3A and 3B are schematic depictions of an exemplary RFID braceletand an annular antenna.

FIG. 4 is a schematic depiction of an exemplary dispensing deviceshowing features designed to block or retard saliva and moistureingress.

FIGS. 5A and B are schematic depictions of an exemplary geometry for adispensing tip of a drug dispensing device.

FIGS. 6A-D are a schematic depiction of an exemplary proboscis of a drugdispensing device wherein the proboscis has an S-shape and comprises ashroud.

FIGS. 7A-B are schematic depictions of an exemplary single doseapplicator (SDA).

FIGS. 8A and 8B are photographs of exemplary multiple dose dispensers,holding a plurality of SDAs (FIG. 8A) and holding a plurality of SDAsand further showing an SDA after removal the multiple dose dispenser(FIG. 8B).

FIGS. 9A-C are schematic depictions of an exemplary multiple dosedispenser holding a plurality of SDAs.

FIGS. 10A-C are schematic depictions of another exemplary multiple dosedispenser holding a plurality of SDAs. Included is a means for sensingwhen each SDA is removed from the device as well as a port which can beplugged into a computer do download user dose history information.

DETAILED DESCRIPTION OF THE INVENTION

The following disclosure describes handheld and portable drug dispensingdevices, systems and methods for their use in oral transmucosaladministration of small volume drug dosage forms. A detailed disclosureof the devices, systems and methods for administration of drug dosageforms are provided hereinbelow. The present invention generallyencompasses: (1) drug dosage forms (tablets); (2) drug dispensingdevices; (3) systems that include a drug dispensing device and a drugdosage form; and (4) methods for using such drug dispensing devices andsystems.

The disclosure is generally directed to dispensing devices fordispensing any of a number of types of small volume dosage forms to theoral mucosa, methods of using such dispensing devices and systemscomprising the same. The invention is not limited to the specificdevices, systems and methodology or syndromes described herein, as thesemay, of course, vary. It is also to be understood that the terminologyused herein is for the purpose of describing particular embodimentsonly, and is not intended to limit the scope of the present invention.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “and”, and “the” include plural references unlessthe context clearly dictates otherwise. Thus, for example, reference to“a drug formulation” includes a plurality of such formulations andreference to “a drug delivery device” includes systems comprising drugformulations and devices for containment, storage and delivery of suchformulations.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood to one of ordinary skill inthe art to which this invention belongs. Although any methods, devicesand materials similar or equivalent to those described herein can beused in the practice or testing of the invention, the preferred methods,devices and materials are now described.

Definitions

The terms “formulation” and “drug formulation” or “drug dosage form” asused herein refer to a physical composition containing at least onetherapeutic agent, which may be provided in any of a number of dosageforms for delivery to a subject. The dosage form may be provided to thepatient as a lozenge, pill, capsule, membrane, strip, liquid, patch,pad, film, gum, gel, spray or other form. In one embodiment, the drugdosage form is a solid, e.g., a lozenge, a pill, a tablet, a membrane ora strip. The claimed “drug dosage forms” are also referred to herein astablets.

The term “drug” as used herein is generally meant to refer to anysubstance that alters the physiology of an animal. The term “drug” maybe used interchangeably herein with the terms “therapeutic agent”,“medication”, “pharmacologically active agent” and the like. It will beunderstood that a “drug” formulation may include more than onetherapeutic agent, wherein exemplary combinations of therapeutic agentsinclude a combination of two or more drugs.

The term “subject” includes any subject, generally a mammal (e.g.,human, canine, feline, equine, bovine, ungulate etc.), adult or child,in which treatment for a disorder is desired. The terms “subject” and“patient” may be used interchangeably herein.

The term “transmucosal” delivery of a drug and the like is meant toencompass all forms of delivery across or through a mucous membrane. Inparticular, “oral transmucosal drug delivery” and “oral transmucosaladministration” as used herein refer to drug delivery that occurssubstantially via the oral transmucosal route and not via swallowingfollowed by GI absorption. This includes delivery via buccal, sublingualand gum transmucosal areas. Transmucosal dosage forms are designed toprovide for a dissolution/erosion rate that allows for maximal deliveryvia the oral mucosa, typically via placement of the dosage form in thesublingual cavity.

As used herein, “sublingual”, means literally “under the tongue” andrefers to a method of administering substances via the mouth in such away that the substances are rapidly absorbed via the blood vessels underthe tongue rather than via the digestive tract. Absorption occurs viahighly vascularized mucosa and allows a substance more direct access tothe blood circulation, providing for direct systemic administrationindependent of gastro-intestinal influences.

The term “treatment” or “management” of a medical disorder or conditionis used herein to generally describe regression, suppression, ormitigation of symptoms of the medical disorder or condition so as tomake the subject more comfortable as determined by subjective criteria,objective criteria, or both.

“Operatively connected” as used herein means the components are providedin a device so as to function as intended to achieve an aim. Forexample, a memory device operatively connected to a CPU which is furtheroperatively connected to a release mechanism may be meant to indicatethat, upon actuation, the CPU communicates with the memory device tocheck the status or history of drug delivery, and then furthercommunicates with the release mechanism (e.g., via a solenoid and aswitch) to release and dispense a drug.

The term “FOB” refers to a small, portable handheld, powered electronicdocking device that can be used in conjunction with the drug dispensingdevice to upload data, download data, control access to the drugdispensing device, control access to the drug dosage forms, or enhanceor otherwise alter the user interface of the drug dispensing device. AFOB may communicate and dock with a drug dispensing device either in awired or wireless fashion. A FOB may be adapted to attach to a cord soas to allow the FOB to hang from the neck of a patient, or healthcareprofessional such as a physician or caregiver, particularly in thehospital setting. A drug dispensing device may communicate with aphysician or care giver via the FOB.

The terms “dispensing device”, “drug dispensing device”, “dispenser”,“drug dispenser”, “drug dosage dispenser” and “drug delivery device”,are used interchangeably herein with the term “dispensing device” andrefer to a device that dispenses a drug dosage form. A single doseapplicator is considered to be a “drug dispensing device”. Thedispensing device provides a mechanism for controlled and safe deliveryof a medication formulated in a dosage form for delivery to the oralmucosa of a patient and is adapted for storage and/or delivery of adosage form such as a lozenge, pill, tablet, capsule, membrane, strip,liquid, patch, film, strip, gel, spray or other form.

The term “systems that include a drug dosage form and a dispensingdevice” as used herein refers to a drug dispensing system for deliveryand/or monitoring of drug administration. A system may be used tomonitor and deliver both efficacious and safe dosages such that theamount of drug delivered, and the corresponding safety and efficacy areenhanced over currently available systems. The system may have one ormore features that provide for improved safety and ease of use overcurrently available systems including a security feature that preventsunauthorized access to the stored drugs, such as a dosing lock-outfeature, a dose counting feature, a memory means for retaininginformation about dose delivery, and an interface for bidirectionalexchange of information with a user, a drug cartridge, or another devicesuch as a computer, as well as a means for identifying a device usersuch as the patient or a health care provider in order to provide forcontrolled drug access.

The term “proboscis” is used interchangeably with the terms “dispensingtip” and “delivery tip”, and refers to a dispensing and/or positioningtip of a drug dispenser that delivers a dosage form to a desiredlocation (e.g. the oral mucosa).

The term “shroud” is used to describe a partial or complete covering ofthe delivery port of the proboscis to protect the delivery port fromcontact with saliva or other moisture in the oral cavity.

Features of Dispensing Devices

One exemplary embodiment of the drug dispensing device is handheld andportable, as shown in FIG. 1. This embodiment of the drug dispensingdevice has a disposable dispensing end 189 and a reusable controller191. In this embodiment, a disposable drug cartridge 17 is locked intoplace when the disposable dispensing end 189, and reusable controllerend 191 are latched to one another (FIG. 2). In another embodiment, thedevice is capable of dispensing multiple drug dosage forms, a singledose at a time for delivery via the oral mucosa, e.g., into thesublingual or buccal space.

The drug dispensing device has a housing with a dispensing end whichtypically has a proboscis with a shroud which can block or retard salivaingress and saliva contact with the tablet exit port, as furtherdescribed herein below.

In some embodiments of the invention, the drug dispensing device ismanually actuated and fully disposable, e.g., a single dose applicator(SDA).

In other embodiments, the drug dispensing device is actuated by anelectromechanical means. The claimed drug dispensing devices have anumber of additional features, further described below.

User Identification Feature

The claimed dispensing devices comprise a detecting means for patientidentification such as: fingerprint identification; RFID detection withthe use of an active or passive RFID tag on a bracelet, necklace, clip,belt, strap, ring, adhesive patch (e.g., on the finger or thumb of thepatient), or an implant, or other means of locating and affixing thetag; retinal identification; DNA identification; voice recognition;password or code entry; physical key; electronic or magnetic key;personal area network identification using the human body or clothing asa data or signal conduit; optical scanner or face recognition; sonic;subsonic or ultrasonic identification; or any other means of identifyingan individual and verifying their identity. The dispensing device mayemploy one or more means to identify the user, enabling the system todetermine if a dispensing request is being made in an authorized orunauthorized manner.

It is important for effective delivery of many drugs to ensure that thedispensing device is not accidentally or intentionally used by anunauthorized individual thus preventing accidental or intentionaldiversion of the drug. Such user identification systems may recognizeone or more users, for example, in an inpatient hospital setting thedispensing device can be programmed to recognize the patient to whom itis prescribed, and/or an authorized healthcare provider such as a nurseor physician.

One method of user identification is the use of a short distance (“nearfield”) passive RFID tag attached to a bracelet, a necklace, an adhesivepatch placed on the end of the patient's finger or thumb, a ring, aclothing tag, an orally mounted device such as an orthodontic retainer,a belt, a strap, some combination of the above, or another location.When an RFID tag is used in the “near field”, roughly defined as about16% of the wavelength of the received signal, the tag behaves in theinductive mode of operation, coupling the reader and tag antennamagnetically. The near field is characterized by at least two features:first, a rapid decline in field strength with distance, and second, astrong directionality of the signal. In the near field, the signalstrength falls off very rapidly, with a signal strength loss ofapproximately 60 dB per decade in distance. Good inductive couplingbetween the transmitter antenna and the RFID tag antenna occurs when twoantennas are oriented in parallel planes with the axes through thecenter of each antenna in close proximity. A second orientation for goodinductive coupling is when the two antennas are oriented in the sameplane, and in close proximity Strong signal strength (robust useridentification) is provided when the device is very close to the RFIDtag (as exemplified by the system shown in FIG. 1; details of a RFIDbracelet embodiment shown in FIG. 3A and details of an RFID antennaembodiment shown in FIG. 3B). At the same time, a very poor signal isprovided when the device is further away or misaligned from the tag,which helps prevent unauthorized use by someone other than the patientwho attempts to use the device. It is preferable to operate in this nearfield region with good antenna alignment. Furthermore, it is preferableto operate with a very short distance of adequate signal strength for apositive identification, so that it is very difficult to receive asignal if the device is not in the proper orientation and proximity tothe RFID tag. To attain a short distance and a proper alignment betweenantennas, the dispensing device may be designed so as to properly locatethe RFID reader antenna, mounted in the dispensing device, adjacent anRFID tag antenna, mounted, for example, on a wrist band or bracelet, afinger or thumb ring, or a clothing tag on the collar, or an adhesivepatch on the hand, arm, cheek, neck, or elsewhere. Furthermore, an RFIDtag antenna on a wrist band or bracelet may be held in proper alignmentand location by means of a small adhesive patch that prevents thebracelet from moving or rotating on the wrist.

RFID technology is widely utilized for inventory, logistical tracking,and other supply chain and related functions. A passive RFID tagincludes a chip and an antenna and when exposed to, and energized by,radio-frequency energy from the RFID reader, the tag transmits itsidentification which is captured by the reader. A tag may have eitherread functionality or read/write functionality. An active RFID tagoperates in the same manner as a passive RFID tag, except it has its ownpower source, such as a battery.

An RFID tag, inlay or label comprises an RFID die or chip component(comprising an electronic identification circuit and a coupling means),a circuit and an antenna structure coupled to the coupling means. Thistag component can be embedded into a bracelet, necklace, ring, adhesivepatch, clothing tag, orally mounted device, belt, strap, or combinationthere of—any of which may be worn by the patient. An exemplary wristworn RFID tag, or bracelet, is shown in FIG. 1 and a detailed embodimentis shown in FIG. 3A. In FIG. 3A, the conductor is wrapped one or moretimes around the wrist such that the antenna axis is effectivelyparallel to the axis of the wrist and forearm. This configuration allowsfor a wrist worn RFID tag such as a bracelet to have a directionalorientation aligned toward a device in the palm of one's hand as shownin FIG. 3A. The fixed orientation allows coupling with the RFID readerhoused within a handheld device. FIG. 3A shows an RFID circuit board179, a coiled conductor antenna 177, an annular antenna on the RFIDbracelet 183, where the annular antenna produces an electromagneticfield directed towards one's hand 181. Providing this directionality isnot possible with existing RFID bracelet technology.

The claimed RFID tag, inlay or label comprises a die or chip, a circuitand antenna that includes one or more wraps of a conductor 187 thatcircumvent the wrist to form a bracelet 173 as shown in FIGS. 1 and 3A.

There is a continuing, unfilled need for devices, methods, and systemscomprising a wrist worn RFID tag which can couple or communicate with ahandheld device permitting patient identification by the handhelddevice. The present invention addresses this need.

In one example of this embodiment, the dispensing device employs a highfrequency RFID reader for use in the inpatient (hospital, clinic, etc.)setting, operating on or near the 13.56 MHz frequency band, and thepatient is fitted with a disposable version of the aforementioned RFIDbracelet with annular antenna designed in such a way that if thebracelet or wrist band is removed, the RFID tag, its antenna, or anothercomponent of the associated circuit is damaged or destroyed, renderingthe bracelet or wrist band non-functional. In one example, the range ofthe RFID communication is short, between 0 inches and 12 inchespreferably, more preferably between 0 and 8 inches, and most preferablybetween 0 and 6 inches.

In one preferred embodiment, the RFID signal is directional andsymmetrical, allowing proper use by the intended patient to betransparent, usable by right or left hands equally, easy and reliable,while at the same time making unauthorized use by another individualdifficult.

In another embodiment, the RFID reader antenna employs a ferrite 185 todirect or focus the field toward the RFID tag, as shown in FIG. 3B. Theferrite antenna is bidirectional but not symmetrical, having a coiledconductor 187, e.g., made of ferrite 185, such that the RFID tag isdesigned to work equally well when the RFID reader device is held ineither the left or right hand (FIG. 3B). Additionally, this ferriteantenna provides for increased range and increased directionality.

Finger or Thumb Patch RFID Tag

In yet another embodiment, the RFID tag is provided as a patch orsticker, which is designed to be attached (adhered) to the end of afinger or the thumb of a patient. The patch or sticker may be attachedto any area around the finger or hand, including the pad side or thenail side of the fingers/thumb. The patch typically comprises amicrochip attached to an antenna which is packaged in a way that itadheres to the end of a finger or the thumb of a patient for the periodof time that a given dispensing device is used by the patient. The tagpicks up signals from and sends signals to a reader contained within adrug dispensing device. The tag contains unique information, specific tothe reader located in the dispensing device it is paired with. Thereader has one or more antennas, which emit radio waves and receivesignals back from the tag. When the finger or thumb patch is heldsufficiently close to the drug dispensing device, the reader receives asignal which enables the dispensing device to dispense a dosage form, solong as the device is not in a timed lock-out period.

Lock Out

In one embodiment, the dispensing device has a timed lock-out featurewhich provides for a set lock out time at regular intervals or timeperiods.

The timed lock-out period for the claimed dispensing device is typicallyfrom 5 minutes to 60 minutes, from 10 minutes to 40 minutes, from 15minutes to 30 minutes, typically 15 or 20 minutes. The timed lock-outperiod may be set at any one minute interval from 5 to 60 minutes, e.g.,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ,16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39,40, 41,42, 43 ,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59or 60 minutes. The lock-out time is typically preset, however, thedispensing device may provide a means for adjusting the lock-out time.

There can also be a second tier lockout, for example a scenario wherethe patient is permitted to take a tablet once every 20 minutes, not toexceed 12 doses in a 24 hour period.

Blocking/Retarding Saliva and Moisture Ingress

In some embodiments, the device comprises a means for minimizing oreliminating saliva ingress and moisture ingress onto and into thedevice: (1) to avoid wetting the dosage forms therein, whether in thedispensing track or in the primary dosage package (cartridge); (2) toisolate any saliva that enters the dispensing device in such a mannerthat the dosage forms therein remain dry; (3) to absorb or adsorb anysaliva that enters the dispensing device in such a manner that thedosage forms remain dry; (4) to block saliva and moisture from enteringthe device, to protect the dosage forms from vapor and liquid phasemoisture; (5) to block incidental contact of the tongue or mucosa on thetablet exit port or proboscis that can lead to wetting and ultimatelythe adherence of the tablet to the device, or (6) any combinationthereof.

The device may also comprise a means for preventing and/or controllinghumidity ingress into and within the device due to ambient conditionsoutside the device. The dispensing device may rely on valves, pads,seals, the rest position of push rod, proboscis design and a shroud tominimize or eliminate saliva ingress or moisture into the dispensingdevice during administration of the dosage forms.

The means for minimizing or eliminating saliva ingress or preventingother moisture from entering the dispensing device includes, but is notlimited to, one or more flexible or rigid seals, valves, one or moreflexible or rigid wipers, use of one or more absorbent materialcomponents such as a desiccant or pad, a door or latch that is manuallyor automatically opened and closed, multiple stage delivery systems, apositive air pressure and airflow, or an air gap or prescribed distanceor barrier/shroud maintained between the tablet delivery orifice and themucus membrane tissues within the mouth that may transport the saliva.The shroud limits the ability of the tongue or oral mucosa to contactthe dosage form dispensing area, thereby controlling saliva contact andingress. By inhibiting or eliminating the “wetness” inside the shroudand on the surface of the valve/seal, the dosage form is dispensedwithout adhesion occurring between the dosage form and the shroud orvalve/seal. In this embodiment, the drug dispensing device provides ameans for minimizing or eliminating saliva ingress into the deviceduring administration of the drug to the oral mucosa of the patient.

Means for trapping or otherwise isolating saliva or moisture once it hasentered the device include, but are not limited to, a hydrophilicwicking material or component, an absorbent or adsorbent material orcomponent, a desiccant material or component, a separate track orchannel for moisture to collect, a separate channel to communicatemoisture to the absorbents or adsorbents, or any combination of thesematerials or components, and are described in detail in U.S. PatentPublication Nos. 20070186923, 20080164275, 20080268023 and PCTPublication Nos. WO 2007/081947, W02008/085763 and W02008/085764, eachof which is expressly incorporated by reference herein.

To protect the drug dosage forms from exposure to moisture either fromhumidity, saliva ingress, or accidental exposure to other water basedliquids, the dispensing device and the container or cartridge whichhouses the dosage form within the device may or may not contain adesiccant. In some embodiments, the design of the dispensing device, inparticular, the proboscis and shroud are sufficient to minimize oreliminate saliva ingress and moisture ingress into the device. In suchcases, there is no desiccant material in the dispensing device. In oneembodiment, the desiccant may snap into a cavity in the side of thecartridge. There are holes in the desiccant cavity that connect it tothe tablet stack, exposing the tablets to desiccant and keeping themdry.

The proboscis design for use in the device is characterized by a distaldevice shape, typically an S-shape, that aids in use of the deviceand/or placement of the tip on the oral mucosa of the subject. The shapetypically has curves, angles, and geometries such that it enables properuse of the device and placement of the dosage form on the oral mucosa ofthe subject, e.g., in the sublingual space. The shroud of the device hasa geometry that forms a barrier between the device and the oral mucosaand tongue, a relief for dosage form delivery, and an interior that ishydrophobic or hydrophilic and serves to minimize or eliminate salivaingress or moisture ingress by creating a barrier from the oral mucosacontacting the valve area and dosage form, aiding in dosage formdispensing and discouraging dosage form adherence to the shroud. Theshroud may have a rounded interior surface or other geometries tomitigate the dosage form adhering to the shroud. The shroud may alsoinclude another component to aid in keeping the interior hydrophobic orhydrophilic by absorbing or adsorbing saliva and moisture in order toinhibit the dosage form from sticking to the surface. The shroud limitsthe ability of the tongue or oral mucosa to contact the dosage formdispensing area, thereby controlling saliva contact and ingress as wellas the wetting of the device tablet exit port.

FIG. 4 is a schematic depiction of an exemplary dispensing devicewherein the dispensing tip comprises a shroud 29 having a one or moreof: a wiping or sealing valve 33 or 35, an absorbent pad 39, a drugdrying chamber/moisture communication channel 43, desiccant in thechannel 45, a cartridge 17 containing dosage forms 67 and desiccant inthe cartridge 47.

FIGS. 5A and B are schematic depictions of an exemplary geometry for adispensing tip that prevents contact of one or more seals 33, 35 withthe moist or wet surface of the oral mucosa via a shroud 29.

FIGS. 6A-D are a schematic depiction of an exemplary proboscis 31 of thedispensing device wherein the proboscis 31 has an S-shape 53 andcomprises a shroud 29, a valve 33 for dispensing a dosage form 67 and acut-out/relief 55 for the dosage form to be placed against the oralmucosa and not moved when the device is withdrawn following dispensing.The shroud shields the valve from moisture and saliva ingress from thetongue and other mucosa and provides an area for the dosage form to exitthe device without “sticking” to the wetted distal valve or shroud area.The valve functions with the shroud to control saliva and moistureingress, as well as aid in delivery of the dosage form.

The claimed drug dispensing may be used to administer a tablet that issensitive to moisture and/or humidity. In some cases, the dispensingdevice includes a tablet cartridge 17 (e.g., as shown in FIG. 2) thatprotects the tablet from liquid and vapor phase moisture, includinghumidity, liquid moisture, saliva, mucus, etc. The cartridge may becylindrical, disk-shaped, helical, rectilinear, non-ordered, or may takethe form of any assemblage of tablets that allows the drug dispensingdevice to dispense them in a controlled manner. To prevent the unusedtablets from absorbing moisture or otherwise becoming exposed tomoisture prior to use, the cartridge may provide a means of sealing thetablets from exposure to moisture. In some embodiments, all of thetablets in a cartridge may be packaged together in a foil sealedcompartment.

In the case of medications, such as sufentanil, that are sensitive tooxygen when provided as a solid tablet, the primary package (e.g., acartridge), may contain the solid sufentanil tablet and an oxygenscavenger, as a means to minimize or eliminate generation of oxidativedegradation products upon storage, as detailed in U.S. patentapplication Ser. No. 12/275,485, expressly incorporated by referenceherein.

The pushrod design of the dispensing device is described in U.S. PatentPublication Nos. 20070186923 and 20080164275, also expresslyincorporated by reference herein.

Dosing History/Feedback

Further embodiments of the device include the ability to storehistorical use information and the ability to transmit such information.The device may be capable of unidirectional (downloading) orbidirectional information transfer. For example, such an exchange ofinformation may be accomplished by downloading stored information to acomputer through a physically wired interface, such as a USB or othercommunication connection. Alternatively, information may be communicatedvia a wireless system, e.g. Bluetooth, Wifi, or other RF technology.

In another embodiment, the dispensing device has a dose counting featurethat monitors and stores the history of drug usage. Such information mayinclude historical use information, for example the number of dosagesstored and dispensed, the state of the dispenser, and the times ofdispensing.

Device Setup

The claimed dispensing device may be capable of self-calibration of thedispense mechanism, or the device may be calibrated manually. Thisprocess may employ a “shipping tablet” as the first tablet dispensedfrom the device. This shipping tablet has a feature or features thatdifferentiate it from a drug-containing tablet and the push rod. Thedifferentiating feature may be physical, optical, RF, electronic ormagnetic. This features can be recognized by the device during setup toensure that the device is working correctly without requiring thedispensing of a drug-containing tablet. This approach also confirms,during setup, that a ‘new cartridge’ is being used.

Additional Features

The claimed dispensing device may also provide the ability to recognizea specific cartridge by a mechanical, optical (e.g. bar code),electronic (e.g. microchip), magnetic, radio frequency, chemical, orother means of detecting and identifying the cartridge. In one exemplaryembodiment of the invention, the cartridge contains a physical keyingdetail on the cartridge that is physically detected by a sensor orswitch or a series of sensors or switches in the dispensing device.Furthermore, the dispensing device may communicate uni-directionally orbi-directionally with the cartridge to exchange information. Suchinformation may include drug name, dosage strength, usage information,lockout period, manufacturing lot number, indications for use, sideeffects, drug interactions, date of manufacture, date of expiration,serial number, number of doses in the cartridge, or any other relevantinformation. The dispensing device may be able to write, in addition toread, information to the cartridge, like date used, health care provideror patient identification, number of doses remaining, etc.

The claimed dispensing device provides mechanical protection for thedosage forms contained therein, preventing breakage, chipping, hydrationetc., thereby allowing for dispensing of the undamaged dosage formscontained therein. This is of particular importance for small fragileand friable dosage forms.

The drug dispensing device may be powered by a battery, capacitor, fuelcell, external electrical power supply, or other power supply source, ormay require no electrical power, but be manually activated.

In some embodiments, the dispensing device is capable of issuing alarmsor other notifications when functional or safety issues arise. The alarmor other notification may trigger an alert on the dispensing device, ona dock or other peripheral device; on a computer or by means of a wiredor wireless network, or may alert other remote devices. The alarm ornotification may be audible, tactile, visual, or may employ other meansof notifying one or more individuals.

Base Station/Docking Station

In some embodiments the drug dispensing system includes a base stationfor recharging one or more drug dispensing devices and a portabledocking FOB between uses. In addition to recharging the drug dispensingdevices and FOBs, the base station may provide one or more of thefollowing functionality: wireless or wired connectivity to a peripheraldevice, computer or network; feedback on the charging state for thedevices being recharges; an interface for viewing, adding, deleting, ormodifying the data on a drug dispensing device or FOB; a means forsynchronizing data between multiple drug dispensing devices and/or FOBs;a means for updating a drug dispensing device; and a means forconducting a diagnostic test on drug dispensing devices and/or FOBs.

A drug dispensing device may communicate with a physician or care giver,via a base station, dock or a wired or wireless communication means.

The dispensing device may employ one or more levels of interface fordifferent types of authorized users, for example the patient, the nurse,the physician, pharmacist or other authorized medical or healthcarepersonnel. These different interfaces may include components such askeypads, buttons, graphical icons and instructions, lights, LED's,monochrome or color graphical or text displays, touch-screens, LCD's,sounds, tactile feedback, voice recognition interfaces, and other inputand output devices and means. The activity, or mode, of the userinterface may be determined by the mode of operation of the dispensingdevice, by a login or access activity by a user such as a password orcode entry, by the connection or disconnection of the dispensing devicefrom a dock, computer, or network, or by the detection of an authorizedaccess key, such as a key, and/or RFID tag, combination, password,barcode, or similar technology. Upon changing the interface mode, thefunctionality of the device may be changed, either activating,inactivating or changing the functionality of the various interfacecomponents described above. By allowing the device to have one or moreinterface modes, with differing functionality associated with each one,the device can be optimized for various uses.

Single Dose Applicators (SDAs) and Multiple Dose Dispensers (MDDs)

The invention further provides dispensing devices and methods of usingthe same for oral transmucosal delivery of a drug dosage form using asingle dose applicator (SDA). Use of the SDA is not limited to anyparticular type of device or patient population. As such, the claimedSDAs find utility in drug delivery to pediatric, adult and non-humanmammalian subjects.

In one embodiment, a SDA is used to administer a variety of drug dosageforms, including a solid tablet, a liquid capsule, a gel capsule, aliquid, a gel, a powder, a film, a strip, a ribbon, a spray, a mist, apatch, or any other suitable drug dosage form.

The SDA may be provided as a pair of forceps, a syringe, a stick or rod,a straw, a pad, a capsule, a cup, a spoon, a strip, a tube, anapplicator, a dropper, a patch, an adhesive pad, an adhesive film, asprayer, an atomizer, or any other form suitable for the application ofa single drug dosage form to the oral mucosa of a subject, e.g., theoral mucosa in the sublingual space. As will be understood by one ofskill in the art, the SDA design may vary, so long as it is effective toplace a drug dosage form, such as a tablet, in the desired location onan oral mucosal membrane, e.g., in the sublingual space, in a mannerthat preserves integrity of the drug dosage form in the dispensingprocess. After use, the SDA is disposed of, so as to eliminate the riskof contaminating the drug dispensing device with saliva, or othercontaminants.

The SDA may contain the dosage form within, may have the drug dosageform attached or affixed to it, may have the dosage form dissolved init, and may afford a seal against moisture, humidity, and light. The SDAmay be manually manipulated by a patient, healthcare provider, or otheruser to place the dosage form in the proper location for drug delivery.The SDA may also be child resistant and/or enable abuse deterrence.

The single-dose applicator is used to deliver tablets or other dosageforms into the hand, the mouth, under the tongue, or to other locationsappropriate for specific drug delivery needs.

In one preferred embodiment, a single-dose applicator or drug dispensingdevice is used to deliver a dosage form directly to the oral mucosa,e.g., the sublingual space.

The dosage form inside the SDA remains dry prior to dispensing, at whichpoint a single dosage form is dispensed onto the oral mucosa, and thepatient's saliva wets the tablet and allows for tabletdisintegration/erosion and drug dissolution. After use, the SDA isdisposed of.

In one approach, for sublingual administration, a small volume dosageform is administered by placement under the tongue, adjacent to thefrenulum with a syringe, a syringe-type SDA, a stick or rod, a straw, adropper, or any other form suitable for the application of a single drugdosage form, including but not limited to a SDA. Numerous examples ofSDAs are described in U.S. patent application Ser. No. 12/187,937 andPCT Publication No. W02008/085765, each of which is expresslyincorporated by reference herein. FIGS. 7A and B provide detaileddrawings of an exemplary SDA; FIG. 7A is an exploded view and FIG. 7B isan assembled view. The embodiment of the device shown in FIGS. 7A and Bconsists of two case halves, 171 and 169, a pusher 165, and a label,209. For assembly, the two case halves are snapped together and thelabel 209 is applied so that the tip 199 is not allowed to deflect whilethe label 209 is still in place, providing one level of child resistantpackaging. The tablet 67 is placed in the cavity between the case halves171 and 169, and the pusher 165 is snapped into place trapping thetablet inside of the assembly. In this configuration as shown in FIG.7A, the snap feature on the pusher 201 keeps the pusher 165 from comingout of the assembly and the raised portion on the pusher 197 baresagainst the edge of the label 209 to keep the pusher from advancing thetablet 67 out of the tip 199 thus acting as an additional level of childresistant packaging. During use, the user first removes the label 209from the assembly. In this configuration, while the label 209 is nolonger present to resist advancement of the pusher 165, there is a smallbridge feature 203 in one or both of the case halves to provide someresistance so that accidental pusher actuation does not occur. Todispense the tablet 67, a user places the tip of the SDA 199sublingually and pushes on the back of the pusher 165 hard enough toovercome the strength of the bridge feature 203. At this time, thebridge feature 203 breaks away and the pusher advances flexing the tipof the SDA 199 open while advancing the tablet out of the device andinto the sublingual space.

In one embodiment, the claimed drug dispensing device contains aplurality of SDAs, provided in a cartridge or individually packagedwhich is designed to dispense a single SDA containing a single drugdosage form for use by the patient, healthcare provider, or user. Thedrug dispensing device may dispense single SDAs and comprise any of anumber of the features described herein which are advantageous to safeand effective dispensing of single drug dosage forms.

A plurality of SDAs may be provided as a series of individual SDAsattached by a backing or housed in a multiple dose dispenser 137 ormultiple dose storage unit. In some cases, SDAs 123 are stored in amultiple dose storage unit which may be referred to as a multiplesingle-dose dispenser (MSD) or multiple dose dispenser (MDD) 137.Exemplary MSDs or MDDs are shown in FIGS. 8A-B, 9A-C, 10A-C, and in U.S.patent application Ser. No. 12/187,937 and PCT Publication No.W02008/085765, each of which is expressly incorporated by referenceherein. In each embodiment for use in dispensing SDAs, the MSD or MDDmay comprise a sensing means 205 for detecting when an SDA is removedfrom the device along with electronics capable of recording and storinginformation as to when the SDA is removed. The MSD or MDD 137 isdesigned to be child resistant. FIGS. 8A-B, 9A-C and 10A-C show aplurality of SDAs 123 in various exemplary MSD or MDD configurations137. As shown in FIG. 9A and 9B, the MSD/MDD may comprise a port 207,which when plugged into a computer allows for the download of storedinformation. See e.g., FIGS. 8A-B, 9A-C and 10A-C, which illustrateexemplary multiple dose applicators 137 for delivering dispensing drugdosage forms, each individually packaged in a SDA 123.

Dosage Forms

The dispensing devices and SDAs described herein provide for single orrepeated dispensing of individual (single) small volume drug dosageforms for oral transmucosal administration to a patient.

The term “small volume drug dosage form” or “small volume dosage form”is used herein with reference to a small volume dosage form or tabletthat has a volume of less than 100 mcl and a mass of less than 100 mg, avolume of less than 30 mcl and a mass of less than 30 mg, or a volume offrom about 3 mcl to about 15 mcl or a mass of from about 3 mg to about15 mg. More specifically, the dosage form has a mass of less than 100mg, 90 mg, 80 mg, 70 mg, 60 mg, 50 mg, 40 mg, 30 mg, 29 mg, 28 mg, 27mg, 26 mg, 25 mg, 24 mg, 23 mg, 22 mg, 21 mg, 20 mg, 19 mg, 18 mg, 17mg, 16 mg, 15 mg, 14 mg, 13 mg, 12 mg, 11 mg, 10 mg, 9 mg, 8 mg, 7 mg, 6mg or 5 mg or a volume of less than 100 mcl, 90 mcl, 80 mcl, 70 mcl, 60mcl, 50 mcl, 40 mcl, 30 mcl, 29 mcl, 28 mcl, 27 mcl, 26 mcl, 25 mcl, 24mcl, 23 mcl, 22 mcl, 21 mcl, 20 mcl, 19 mcl, 18 mcl, 17 mcl, 16 mcl, 15mcl, 14 mcl, 13 mcl, 12 mcl, 11 mcl, 10 mcl, 9 mcl, 8 mcl, 7 mcl, 6 mclor 5 mcl.

In one embodiment, when subjected to an in vitro dissolution test in aType II USP dissolution apparatus, about 75%, 80%, 85%, 90%, 95% or moreof the total amount of sufentanil in the tablet is released within 8 or10 minutes. In another embodiment, when subjected to an in vitrodissolution test in a Type II USP dissolution apparatus, about 75%, 80%,85%, 90%, 95% or more of the total amount of sufentanil in the tablet isreleased within 12 minutes.

The “dosage forms” may be administered with a drug dispensing device orSDA, typically have bioadhesive characteristics and may form a hydrogelupon contact with an aqueous solution. The “small volume drug dosageform” or “small volume dosage form may be referred to as a “NanoTab™”.

A dosage form delivered using the drug dispensing devices and SDAsdescribed herein finds utility in oral transmucosal administration ofany drug that can be absorbed via the transmucosal route and can benefitfrom this route of administration, for example if the drug issusceptible to GI or first-pass metabolism.

In one aspect, the device or SDA contains a dosage form comprising fromabout lmcg to 10 mg of a drug, from about 2 mcg to about 1 mg, fromabout 5 mcg to about 200 mcg of a drug or from about 10 mcg to about 100mcg of a drug. Typically the drug will be used for the treatment ofpain.

In another aspect, the dosage from comprises an opioid selected from thegroup consisting of sufentanil, alfentanil, fentanyl, lofentanil,carfentanil, remifentanil, trefentanil, and mirfentanil.

In one exemplary embodiment, the claimed oral transmucosal drug dosageform contains from about 0.25 mcg to about 200 mcg of sufentanil, fromabout 5 mcg to 150 mcg of sufentanil, from about 10 mcg to 100 mcg ofsufentanil, or from about 10 mcg to about 30 mcg of sufentanil. A singleSDA may include dosage forms comprising different amounts of sufentanil.Sufentanil may be provided as sufentanil citrate, sufentanil base, or acombination thereof.

Solid Sufentanil Dosage Forms

In general, small volume solid dosage forms containing from about 2 mcgto about 200 mcg of sufentanil may be used for oral transmucosal drugdelivery. The dosage forms contain sufentanil, alone or in combinationwith another drug, e.g., a benzodiazepine such as triazolam.

The process for manufacture of solid dosage forms, e.g., tablets, pills,capsules, strips, films, powders, lozenges, membranes, patches, film orother forms, comprising sufentanil, typically involves the use of anaqueous and/or organic solvent.

The dosage forms comprise a formulation that is neither effervescent nordoes it comprise an essentially water-free, ordered mixture ofmicroparticles of drug adhered to the surface of carrier particles,where the carrier particles are substantially larger than themicroparticles of drug.

Typical formulations for preparation of sufentanil-containing soliddosage forms and methods of making them are described in U.S. PatentPublication Nos. 20070207207 and 20080166404, expressly incorporated byreference herein. An exemplary formulation for use in making asufentanil-containing solid dosage form is bioadhesive and comprisesfrom about 0.04% to about 4% sufentanil, from about 0.08% to about 1.7%sufentanil or from abut 0.1% to about 2.0% sufentanil, e.g., about0.04%, 0.08%, 0.1%, 0.2%, 2.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%,0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.1%, 1.2%,1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.2%, 2.2%, 2.4%, 2.5%,2.6%, 2.8%, 3.0%, 3.2%, 3.5% or 4% sufentanil.

Numerous suitable nontoxic pharmaceutically acceptable carriers for usein sufentanil-containing solid dosage forms can be found in Remington'sPharmaceutical Sciences, 17th Edition, 1985.

Systems For Administration Of Dosage Forms To A Patient

In one exemplary embodiment, the present invention provides a system,comprising: (1) a dispensing device or SDA for administration of a drugdosage form to the oral mucosa of a subject, for example, a small-volumedosage form or NanoTab™; (2) a dosage form for oral transmucosaladministration, such as a small-volume dosage form or NanoTab™; and (3)a subject.

In another exemplary embodiment, the system for administration of dosageforms to a patient using the claimed drug dispensing device furtherincludes a drug dispensing device wherein the dispensing devicecomprises a means for patient identification and/or a lock-out feature.

Additional features which may be included in the system includes adocking station or other docking means, a means of communication with acomputer network such as a bidirectional communication link with a localor remote computer system (wired or wireless), a pharmaceutical networkmonitoring and control apparatus, a computer network that stores,records and transits information about drug delivery from the device andone or more user interfaces.

Utility

Exemplary conditions treatable with the claimed dispensing devices andSDAs, include but are not limited to acute pain, post operative pain,cancer breakthrough pain, procedural pain and anxiety, nausea and/orvomiting.

One use for the claimed drug dispensing device arises in the inpatientsetting. For example, the need for rapid treatment of acute pain occursin many different clinical situations, including pain following anaccident; post-operative pain; rheumatoid arthritis; back injury;cancer; etc. in the hospital setting. Post-operatively, for example,patients suffer from severe pain for the first few days followed by daysof mild to moderate levels of pain.

In one embodiment of the invention, a cartridge for use in the device inthe inpatient or outpatient setting may hold sufficient drug dosageforms for a single day or multiple 1-5 days of treatment, e.g., 40tablets useful for up to 48 hours of treatment.

In another embodiment the drug dispensing device is comprised of adisposable drug cartridge, a disposable dispensing end, a reusablecontroller end, a user identification means like an RFID tag, a portabledocking FOB for controlling and accessing the drug dispensing device,and a base station for recharging the reusable dispensing end and theportable docking FOB. In this embodiment the drug cartridge is loadedinto the disposable dispensing end, which, in turn, is connected to thereusable controller end and affixed together. This assembly completesthe drug dispensing device which is capable of dispensing dosage formsto the patient upon request, providing a lockout period between dosing,recording dosing and usage history, and allowing this history and thedrug dispensing device settings to be reviewed or electronicallydownloaded. An RFID tag would be affixed to a patient so as to provide awireless identification means that would enable the drug dispensingdevice to operate properly when in proximity to the correct RFID tag. Ahealthcare provider could use the portable docking FOB to dock with thedrug dispensing device, allowing access to settings, controls, history,and other features. When not in use, the reusable controller end and theportable docking FOB could be placed in the base station to recharge thebatteries or power supply.

In yet another embodiment, the drug dispensing device comprises adisposable drug cartridge containing 40 tablets and useful for up to 48hours of treatment, a disposable dispensing end, a reusable controllerend, a user identification means like a directional RFID tag, a lockoutfeature (e.g., with a set lockout time of 20 minutes) and a base stationfor recharging the reusable dispensing end. In this embodiment, thecontroller contains a user interface that can be used to upload datafrom the device, download data such as dosing history or the number oftablets remaining in the cartridge, control access to the drugdispensing device, control access to the drug dosage forms, controlaccess to a tether or other connectable apparatus, and communicatebidirectionally with a hospital computer system or other computernetwork by means of a wired or wireless connection. In this embodiment,the drug cartridge is loaded into the disposable dispensing end, which,in turn, is connected to the reusable controller end and affixedtogether and the dispensing end and cartridge are disposable. Whenoutside the lockout window, the drug dispensing device is capable ofdispensing dosage forms to a patient upon request when the patientpushes a “dispense button”. The dispensing device can record dosing andusage information, and is capable of allowing the information and thedrug dispensing device settings to be reviewed or electronicallydownloaded. In one approach, a directional RFID tag is affixed to thepatient so as to provide a wireless identification means that wouldenable the drug dispensing device to operate properly when in proximityto the correct RFID tag. In other approaches, a different patientidentification means such as fingerprint matching is employed. In eithercase, a healthcare provider interacts directly with the controller endto adjust settings, controls, download usage information, etc. When notin use, the reusable controller end is placed in the base station torecharge the batteries.

When used in the inpatient setting, the claimed dispensing device offersseveral features and advantages over the state of the art in patientdrug administration. The dispensing device allows healthcare providersto provide drug dosage forms to a patient for self administration of PRN(“Pro Re Nata”) medications. PRN refers to drugs that are taken asneeded, such as for pain, nausea, constipation, anxiety, etc. Theclaimed drug dispensing device may be used to dispense any PRNmedication in any drug dosage form in the inpatient setting affordingany combination of the features set forth above, as described in U.S.Patent Publication No. 20070299687.

In another embodiment, a MSD comprising thirty (30) SDAs is prescribedfor a patient who is subjected to an outpatient surgical procedure at aclinic. The patient self administers the first drug dosage form with theassistance of a caregiver while at the clinic, then takes the MSD homefor self administration of one or more doses of the drug.

The claimed dispensing device may also be used in the outpatient settingor in both the inpatient and outpatient setting, e.g., for treatment ofpost operative pain or cancer breakthrough pain. Further examples ofoutpatient indications where the claimed dispensing device finds utilityinclude pain associated with physical trauma, chronic pain, chronicbreakthrough pain, anxiety, insomnia, hypertension, coronary arterydisease, depression, psychosis, addiction, ADHD, high blood pressure,diabetes, constipation, nausea, vertigo and others. See, e.g., U.S.Patent Publication No. 20070260491

To effectively assist in the dispensing of drugs in the acute outpatientsetting, the dispensing device may provide some or all of the followingfeatures: allow the patient to self administer the medication; recorddosing history; allow the dosing history to be read or transferred to acomputer, network or other electronic device; deter tampering ordiversion; have child safety; have lockout; deliver the drug dosage formto the appropriate location (e.g. sublingual, or buccal); record adosing administration or a temperature or humidity event.

When used in the outpatient acute setting (home, office, field, etc.),the dispensing device offers several features and advantages over thestate of the art in outpatient drug administration. The dispensingdevice allows individuals to self administer drugs in accordance withphysician, healthcare provider, or drug label guidelines. The drugdispensing devices, SDAs, methods and systems described herein findutility in this setting. A patient may transition from the inpatientenvironment where a drug dosage form is delivered using the dispensingdevice (e.g., as shown in FIGS. 1-2 and 4-6) to the outpatient settingwhere the same drug dosage form is administered using an SDA/MSD (e.g.,as shown as in FIGS. 7-10). This allows a patient to move from theinpatient to the outpatient setting without having to switchmedications.

All publications mentioned herein are incorporated herein by referencein their entirety for the purpose of describing and disclosing thecompositions and methodologies which are described in the publicationswhich might be used in connection with the presently describedinvention. The publications discussed herein are provided solely fortheir disclosure prior to the filing date of the present application.Nothing herein is to be construed as an admission that the invention isnot entitled to antedate such a disclosure by virtue of prior invention.

Although the foregoing has been described in some detail by way ofillustration and example for purposes of clarity and understanding, itwill be apparent to those skilled in the art that certain changes andmodifications may be practiced. Various aspects of the invention havebeen achieved by a series of experiments, some of which are described byway of the following non-limiting examples. Therefore, the descriptionand examples should not be construed as limiting the scope of theinvention, which is delineated by the appended description of exemplaryembodiments.

1.-34. (canceled)
 35. An apparatus, comprising: a housing defining anactuation pathway; a delivery member, at least a portion of the deliverymember being disposed within the actuation pathway such that a distalend portion of the delivery member and a distal end portion of thehousing define a volume configured to contain a drug-containing tablet,the delivery member configured to move relative to the housing in adistal direction to expel the drug-containing tablet from the volume,the delivery member including a protrusion configured to engage aportion of the housing to limit movement of the delivery member relativeto the housing in a proximal direction; and a safety member removablycoupled the housing, the safety member configured to limit movement ofthe delivery member relative to the housing in the distal direction. 36.The apparatus of claim 35, wherein the safety member is a label coupledto the distal end portion of the housing.
 37. The apparatus of claim 35,wherein: the protrusion is a first protrusion, the delivery memberincluding a second protrusion, the portion of the delivery member beingdisposed within the actuation pathway such that the second protrusioncontacts an edge of the safety member to limit movement of the deliverymember relative to the housing in the distal direction.
 38. Theapparatus of claim 35, wherein, the housing defines a channel incommunication with the actuation pathway; and the delivery memberincludes an elongate protrusion slidably disposed within the channel, anedge of the elongate protrusion configured to limit movement of thedelivery member relative to the housing in the distal direction.
 39. Theapparatus of claim 35, wherein the distal end portion of the housing isconfigured to deform when the delivery member is moved in the distaldirection relative to the housing to produce an opening through whichthe drug-containing tablet can be expelled.
 40. The apparatus of claim35, wherein: the distal end portion of the housing is configured todeform when the delivery member is moved in the distal directionrelative to the housing to produce an opening through which thedrug-containing tablet can be expelled; and the safety member isconfigured to inhibit deformation of the delivery member.
 41. Theapparatus of claim 35, wherein: the housing includes a bridge configuredto engage the delivery member, the bridge configured to be separatedfrom the housing when the delivery member is moved relative to thehousing in the distal direction.
 42. The apparatus of claim 35, furthercomprising: a drug-containing tablet disposed in the volume, thedrug-containing tablet including a dosage of sufentanil.
 43. Theapparatus of claim 42, wherein the drug-containing tablet includes anamount of sufentanil selected from the group consisting of 5 mcg, 10mcg, 15 mcg, 20 mcg, 30 mcg, 40 mcg, 50 mcg, 60 mcg, 70 mcg, 80 mcg and100 mcg, and wherein said drug-containing tablet has a volume of lessthan 30 microliters or a mass less than 30 mg.
 44. The apparatus ofclaim 35, wherein the housing and delivery member are configured toenable a user to deliver a drug-containing tablet to a sub-lingualmucosal membrane.
 45. The apparatus of claim 35, wherein: the distal endportion of the delivery member includes a geometric surface configuredto engage the distal end portion of the housing when the delivery memberis moved in the distal direction relative to the housing to deform thedistal end portion of the housing to produce an opening through whichthe drug-containing tablet can be expelled.
 46. An apparatus,comprising: a housing defining an actuation pathway; a delivery member,at least a portion of the delivery member being disposed within theactuation pathway such that a distal end portion of the delivery memberand a distal end portion of the housing define a volume configured tocontain a drug-containing tablet, the delivery member configured to moverelative to the housing in a distal direction to expel thedrug-containing tablet from the volume, the distal end portion of thehousing is configured to deform when the delivery member is moved in thedistal direction to produce an opening through which the drug-containingtablet can be expelled; and a safety member removably coupled thehousing, a first portion of the safety member configured to limitdeformation of the distal end portion of the housing, a second portionof the safety member configured contact a portion of the delivery memberto limit movement of the delivery member relative to the housing in thedistal direction.
 47. The apparatus of claim 46, wherein the safetymember is a label, the first portion of the label is disposed about thedistal end portion of the housing.
 48. The apparatus of claim 46,wherein: the delivery member includes a protrusion, the portion of thedelivery member being disposed within the actuation pathway such thatthe protrusion limits movement of the delivery member relative to thehousing in the distal direction.
 49. The apparatus of claim 46, wherein,the housing defines a channel in communication with the actuationpathway; and the delivery member includes a protrusion slidably disposedwithin the channel, the protrusion configured to limit movement of thedelivery member relative to the housing in the distal direction.
 50. Theapparatus of claim 46, wherein: the housing includes a breakable memberconfigured to engage the delivery member, the breakable memberconfigured to resist movement of the delivery member relative to thehousing in the distal direction, the breakable member configured todeform when a force applied by the delivery member in the distaldirection exceeds a predetermined threshold.
 51. The apparatus of claim46, wherein the delivery member includes a protrusion configured toengage a portion of the housing to limit movement of the delivery memberrelative to the housing in a proximal direction.
 52. The apparatus ofclaim 46, further comprising: a drug-containing tablet disposed in thevolume, the drug-containing tablet including a dosage of sufentanil. 53.An apparatus, comprising: a housing defining an actuation pathway, thehousing including a breakable member; a delivery member, at least aportion of the delivery member being disposed within the actuationpathway such that a distal end portion of the delivery member and adistal end portion of the housing define a volume configured to containa drug-containing tablet, the delivery member configured to moverelative to the housing in a distal direction to expel thedrug-containing tablet from the volume through an opening defined by thedistal end portion of the housing, the delivery member including a firstprotrusion configured to engage a portion of the housing to limitmovement of the delivery member relative to the housing in a proximaldirection, the delivery member configured to engage the breakable membersuch that the breakable member deforms when a force applied by thedelivery member in the distal direction exceeds a predeterminedthreshold; and a safety member removably coupled the housing, the safetymember configured to limit movement of the delivery member relative tothe housing in the distal direction.
 54. The apparatus of claim 53,wherein the distal end portion of the housing is configured to deformwhen the delivery member is moved in the distal direction to expand theopening.
 55. The apparatus of claim 53, wherein: the distal end portionof the delivery member includes a geometric surface configured to engagethe distal end portion of the housing when the delivery member is movedin the distal direction relative to the housing to deform the distal endportion of the housing to produce the opening.
 56. The apparatus ofclaim 53, wherein: the distal end portion of the housing is configuredto deform when the delivery member is moved in the distal direction toexpand the opening; and a portion of the safety member is configured tolimit deformation of the distal end portion of the housing.
 57. Theapparatus of claim 53, further comprising: a container configured to atleast partially contain the housing, the container including a sensorconfigured to detect when the housing is removed from the container. 58.The apparatus of claim 57, wherein: the housing is a first housing froma plurality of housings, the container is configured to contain theplurality of housings.
 59. The apparatus of claim 57, wherein thecontainer includes: a memory configured to store data associated withthe removal of the housing; and a port configured to operatively couplethe memory to a computer.